PARP1

PARP1 is a chromatin-associated enzyme, polytransferase. As one of 5 confirmed PARPs, PARP1 is the most abundant and highly expressed enzyme. Poly polymerase catalyzes the post-translational modification of proteins by the addition of multiple ADP-ribose moieties. PARP transfers ADP-ribose from nicotinamide dinucleotide (NAD) to glu/asp residues on the substrate protein, and also polymerizes ADP-ribose to form long/branched chain polymers. PARP1 detects and relocates to single strand breaks or nicks in chromosomal DNA. PARP1 is thought to play an important role in the initiation of the DNA repair pathway, although high levels of activation are also associated with increased apoptosis in response to genotoxic stress. In addition, PARP1 may also operate downstream of the Raf-MEK-ERK pathway through direct interaction with ERK2 in the nucleus in a mechanism DNA damage. PARP1 is involved in the base excision repair pathway, by catalyzing the polyation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. It is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, PARP1 may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes.

PARP1 Related Areas

 

PARP1 Alternative Names

PARP-1, PARP, PARP1, ADPRT, ADPRT1, RP11-125A15.2, PPOL, pADPRT-1 [Homo sapiens]
parp-1, PARP, Parp1, Adprp, Adprt1, 5830444G22Rik, AI893648, C80510, PPOL, sPARP-1 [Mus musculus]

Summaries for PARP1

Entrez Gene summary for PARP1:

This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes.

OMIM - description for PARP1:

The chromatin-associated enzyme poly(ADP-ribose) polymerase (ADPRT; EC 2.4.2.30) uses NAD as substrate to catalyze both the covalent transfer of ADP-ribose to a variety of nuclear protein acceptors and subsequently the transfer of an additional 60 to 80 ADP-ribose units to the initial moiety. Nuclear proteins that become predominantly poly(ADP-ribosyl)ated include nucleosomal core histones, histone H1 (see 142711), HMG proteins (see 163910), and topoisomerases I (126420) and II (see 126430). ADP ribosyltransferase is required for cellular repair. Inhibitors of this enzyme potentiate the lethal effects of noxious agents. During repair, NAD+ is consumed and the NAD+ content of the cell decreases. Concomitantly, nuclear proteins are ADP-ribosylated. The enzyme is induced by single-strand breaks in DNA which serve as cosubstrate for the reaction.

Wikipedia summary for PARP1:

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene.

Human PARP1 Protein General Information

 

• Protein names: Poly [ADP-ribose] polymerase 1, Short name=PARP1
• Sequence length: 1014 AA.
• Domain: Repeat Zinc-finger
• Sequence similarities: Contains 1 BRCT domain. Contains 1 PARP alpha-helical domain. Contains 1 PARP catalytic domain. Contains 2 PARP-type zinc fingers.
• Post-translational modification: Phosphorylated by PRKDC and TXK. Phosphorylated upon DNA damage, probably by ATM or ATR. Poly-ADP-ribosylated by PARP2. Poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites.
• Subunit structure: Component of a base excision repair (BER) complex, containing at least XRCC1, PARP2, POLB and LRIG3. Homo- and heterodimer with PARP2. Interacts with PARP3, APTX and SRY. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with TIAM2 and ZNF423 By similarity. Interacts (when poly-ADP-ribosylated) with CHD1L. Interacts with the DNA polymerase alpha catalytic subunit POLA1; this interaction functions as part of the control of replication fork progression. Interacts with EEF1A1, RNF4 and TXK.
• Subcellular location: Nucleus

General information above from UniProt

Function for PARP1 Protein

UniProtKB:

Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.

Genatlas:

• PARP1catalyzes the synthesis of cellular poly(ADP-ribose) following DNA damage
• PARP1 major acceptor for ADP-ribose polymers in an automodification reaction, while histone and other DNA-binding proteins (like HMG, topoisomearase I and II proteins) are also modified to a lesser extent, inducing changes in chromatin structure
• NAD(+)-dependent enzyme that plays a multifunctional role in DNA damage detection and repair and maintenance of genomic stability
• PARP1 limitating of malignant transformation
• PARP1 is involved in necrotic cell death by ATP depletion
• PARP1 is involved in neuron survival in brain development
• together with XRCC1 and APTX, plays an essential role in single-strand DNA break repair
• with SET, may function by physically removing chromatin-bound DEK
• PARP1 regulate the expression of surfactant protein B, a protein required for lung function
• PARP1 acting as positive regulators of genomic stability in eukaryotic cells
• TERF2-associated poly(ADP-ribose)polymerase that protects eroded telomeres
• PARP1 may play a critical role in the regulation of BRCA2 transcription (binds to the BRCA2 promoter in a sequence-specific manner and negatively regulates BRCA2 expression)
• PARP1 plays a role in acute inflammatory diseases
• PARP1 catalyzes poly(ADP-ribosyl)ation of the acceptor proteins using NAD (+) as a substrate
• PARP1 plays a role in acute inflammatory diseases
• PARP1 modifies important regulatory lysines of the core histone tails, which are known to control chromatin structure and function
• PARP1 can modify itself and other chromatin-associated proteins, thereby loosening chromatin to facilitate gene transcription
• negative regulator of CKB at the basal level and during TNFSF11-induced osteoclastogenesis
• negatively regulates the CKB expression at the basal level and TNFSF11 treatment induces degradation of PARP1 and thus increases the CKB expression
• ADP-ribosylation of SMAD proteins by PARP1 is a key step in controlling the strength and duration of SMAD-mediated transcription

Homology for human PARP1

• homolog to rattus Parp1 (91.9 pc)
• homolog to murine Parp1 (92.6 pc)

Phenotype Information for PARP1

• Gene/Locus: PARP1, ADPRT, PPOL, PARP
• Phenotype: Xeroderma pigmentosum

Phenotype Information for PARP1 from OMIM (Online Mendelian Inheritance in Man)

Drugs for PARP1

Drugs for PARP1 from TTD (Therapeutic Targets Database)